title: MS/MS networking guided analysis of molecule and gene cluster families.
abstract: The ability to correlate the production of specialized metabolites to the genetic capacity of the organism that produces such molecules has become an invaluable tool in aiding the discovery of biotechnologically applicable molecules. Here, we accomplish this task by matching molecular families with gene cluster families, making these correlations to 60 microbes at one time instead of connecting one molecule to one organism at a time, such as how it is traditionally done. We can correlate these families through the use of nanospray desorption electrospray ionization MS/MS, an ambient pressure MS technique, in conjunction with MS/MS networking and peptidogenomics. We matched the molecular families of peptide natural products produced by 42 bacilli and 18 pseudomonads through the generation of amino acid sequence tags from MS/MS data of specific clusters found in the MS/MS network. These sequence tags were then linked to biosynthetic gene clusters in publicly accessible genomes, providing us with the ability to link particular molecules with the genes that produced them. As an example of its use, this approach was applied to two unsequenced Pseudoalteromonas species, leading to the discovery of the gene cluster for a molecular family, the bromoalterochromides, in the previously sequenced strain P. piscicida JCM 20779(T). The approach itself is not limited to 60 related strains, because spectral networking can be readily adopted to look at molecular family-gene cluster families of hundreds or more diverse organisms in one single MS/MS network.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Don Duy
authors.initials: DD
authors.lastname: Nguyen
authors.forename: Cheng-Hsuan
authors.initials: CH
authors.lastname: Wu
authors.forename: Wilna J
authors.initials: WJ
authors.lastname: Moree
authors.forename: Anne
authors.initials: A
authors.lastname: Lamsa
authors.forename: Marnix H
authors.initials: MH
authors.lastname: Medema
authors.forename: Xiling
authors.initials: X
authors.lastname: Zhao
authors.forename: Ronnie G
authors.initials: RG
authors.lastname: Gavilan
authors.forename: Marystella
authors.initials: M
authors.lastname: Aparicio
authors.forename: Librada
authors.initials: L
authors.lastname: Atencio
authors.forename: Chanaye
authors.initials: C
authors.lastname: Jackson
authors.forename: Javier
authors.initials: J
authors.lastname: Ballesteros
authors.forename: Joel
authors.initials: J
authors.lastname: Sanchez
authors.forename: Jeramie D
authors.initials: JD
authors.lastname: Watrous
authors.forename: Vanessa V
authors.initials: VV
authors.lastname: Phelan
authors.forename: Corine
authors.initials: C
authors.lastname: van de Wiel
authors.forename: Roland D
authors.initials: RD
authors.lastname: Kersten
authors.forename: Samina
authors.initials: S
authors.lastname: Mehnaz
authors.forename: René
authors.initials: R
authors.lastname: De Mot
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Shank
authors.forename: Pep
authors.initials: P
authors.lastname: Charusanti
authors.forename: Harish
authors.initials: H
authors.lastname: Nagarajan
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Duggan
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
authors.forename: Nuno
authors.initials: N
authors.lastname: Bandeira
authors.forename: Bernhard Ø
authors.initials: BØ
authors.lastname: Palsson
authors.forename: Kit
authors.initials: K
authors.lastname: Pogliano
authors.forename: Marcelino
authors.initials: M
authors.lastname: Gutiérrez
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
mesh_terms: D000595:Amino Acid Sequence; D001407:Bacillus / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D011549:Pseudomonas / Q000235:genetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001426:Bacterial Proteins; D010455:Peptides
keywords: MS/MS molecular networking; mass spectrometry; microbial ecology